Levonorgestrel Intrauterine Contraceptive System Research Articles

Proliferation of the Fallopian Tube Fimbriae and Cortical Inclusion Cysts: Effects of the Menstrual Cycle and the Levonorgestrel Intrauterine Contraceptive System.

The objectives of this study were (i) to explore whether differences in cell proliferation may help explain why most high-grade serous ovarian cancers (HGSOC) arise in the fallopian tube fimbriae (FTF) rather than in ovarian cortical inclusion cysts (CIC); (ii) to compare premenopausal and postmenopausal FTF proliferation as a reason why the age incidence of HGSOC increases at a slower rate after menopause; and (iii) to compare FTF proliferation in cycling women and women using the levonorgestrel intrauterine contraceptive system (Lng-IUS) to see whether proliferation on the Lng-IUS was lower. We studied 60 women undergoing a salpingo-oophorectomy. We used Ki67, paired-box gene 8 (PAX8, Müllerian marker), and calretinin (mesothelial marker) to study FTF and CIC proliferation. FTF Ki67%+ was greater in the follicular than in the luteal phase (4.9% vs. 1.5%; P = 0.003); postmenopausal Ki67%+ was 1.7%. Ki67%+ in PAX8 negative (PAX8-) CICs was extremely low. Proliferation in PAX8+ CICs did not vary by menstrual phase or menopausal status. Follicular Ki67%+ was 2.6-fold higher in FTF than PAX8+ CICs. FTF Ki67%+ from 10 women using the Lng-IUS was not lower than in cycling women. Overall FTF Ki67%+ is greater than overall CIC Ki67%+. Overall FTF Ki67%+ in postmenopausal women is lower than in premenopausal women. The Lng-IUS is not associated with lower FTF Ki67%+. Ki67%+ provides an explanation of the preponderance of FTF-derived HGSOCs, and of the slower increase of HGSOCs after menopause. The Lng-IUS may not be associated with a protective effect against HGSOCs.

Effect of hysteroscopic endometrial electrotomy in treatment of patients with refractory dysfunctional uterine bleeding

Objective To explore the effect of hysteroscopic endometrial electrotomy in the treatment of patients with refractory dysfunctional uterine bleeding. Methods A total of 98 patients with refractory dysfunctional uterine bleeding were selected and randomly divided into control group and study group, with 49 cases in each group. Patients in the control group were treated with levonorgestrel intrauterine contraceptive system in the vagina, while patients in the study group were treated with hysteroscopic endometrial electrotomy. The endometrial thickness, menstrual volume, sex hormone indexes ［serum luteinizing hormone(LH), estradiol(E2), follicle stimulating hormone(FSH)］, hemoglobin level(Hb)and adverse reactions were compared between the two groups before treatment and 6 months after treatment. Results After 6 months of treatment, the endometrial thickness and menstrual volume of the study group were significantly smaller and less than those of the control group(P<0.01). After 6 months of treatment, the levels of LH and FSH in the control group were significantly higher than those in the study group(P<0.01), and the level of E2 was significantly lower than that in the study group(P<0.01). After 6 months of treatment, the Hb level in the study group was significantly higher than that in the control group(P<0.01). The incidence rate of adverse reactions in the study group was 2.04%, which was significantly lower than 16.33% in the control group(P=0.014). Conclusion Hysteroscopicendometrial electrotomy is effective in the treatment of patients with refractory dysfunctional uterine bleeding, which can not only effectively improve the symptoms of patients, correct the level of Hb, but also has no significant impact on the levels of sex hormones.

A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population

ObjectiveThe objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. Study designAn open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18–40 years with regular menstrual cycles (21–35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. ResultsThe full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15–0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4–1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as “none” or “mild” in 91.9% of women. ConclusionsLNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. ImplicationsIn this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region.

Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use

ObjectiveTo evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. Study designIn this Phase III study, 2885 nulliparous and parous women aged 18–35 years were randomized to LNG‐IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. ResultsFrom August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. ConclusionIn this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG‐IUS 12 offers women a low-dose contraceptive option for up to 5 years.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women.Methods: Nulliparous and parous women (aged 18–29 years) with regular menstrual cycles (21–35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit.Results: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being ‘very satisfied’ or ‘satisfied’ with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group.Conclusions: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

A Phase III, single-arm study of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg) in postmenarcheal adolescents

ObjectiveTo assess the safety profile of the low-dose levonorgestrel intrauterine system (LNG-IUS) total content 13.5mg (average approximate release rate 8μg/24h over the first year; LNG-IUS 8; Jaydess®) in adolescents. Study designIn a Phase III study in 36 European centers, 304 healthy nulliparous or parous postmenarcheal adolescents (12–17years) received LNG-IUS 8 for 12months. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included: serious TEAEs, adverse events of special interest, overall user satisfaction, discontinuation rate at 12months, and Pearl Index. ResultsLNG-IUS 8 placement was successful in 303/304 participants (99.7%). Overall, 82.6% of participants reported TEAEs, and serious TEAEs and serious study drug-related TEAEs were reported by 7.6% and 1.0% of participants, respectively. No cases of pelvic inflammatory disease, ectopic pregnancy, or uterine perforation were reported. No pregnancies were reported during the 12-month study. At Month 12/study end, the overall user satisfaction rate was 83.9%. Overall, 51 participants (16.8%) prematurely discontinued the study before 12months; 13.8% of participants discontinued owing to TEAEs. ConclusionsNo new or unexpected safety events were associated with the low-dose LNG-IUS 8. The safety profile of LNG-IUS 8 in adolescents was consistent with that previously reported in adults. The high overall user-satisfaction rate at study end and the low discontinuation rate over 12months demonstrate that LNG-IUS 8 is a highly acceptable contraceptive method among adolescents. ImplicationsThis study is the first to assess the low-dose levonorgestrel intrauterine system LNG-IUS 8 (average approximate release rate 8μg/24h over the first year and total content 13.5mg) specifically in females<18years of age and confirms the safety and efficacy of LNG-IUS 8 in an adolescent population.

A 12-month, Phase III study of a low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg) in postmenarcheal adolescents: an evaluation of placement ease and pain, bleeding and dysmenorrhea

The primary study objective was to assess the safety of a low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg; Skyla® in the US, Jaydess® elsewhere) in adolescents (presented previously[Gemzell-Danielsson et al. Fertil Steril 2014;102:e12-13]). Here, we evaluate ease of placement and placement-related pain, bleeding profile and dysmenorrhea.

Phase III study of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS19.5mg) over 5 years of use: evaluation of bleeding and dysmenorrhea

Phase III study of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS19.5mg) over 5 years of use: evaluation of bleeding and dysmenorrhea

A randomized phase III study comparing a new 13.5 mg levonorgestrel intrauterine contraceptive system with a combined oral contraceptive: analysis of efficacy and bleeding profiles

To compare contraceptive efficacy and bleeding profiles associated with use of the 13.5 mg (total content) levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg) and a 30 μg ethinyl estradiol and 3 mg drospirenone combined oral contraceptive (COC) in younger women.

A 12-month multicenter, randomized phase III study comparing a 13.5 mg levonorgestrel intrauterine contraceptive system with the etonogestrel subdermal contraceptive implant in women aged 18–35 years

To compare 12-month rates of discontinuation (primary outcome), user satisfaction and adverse events (AEs) (secondary outcomes) associated with the use of a new 13.5 mg (total content) levonorgestrel intrauterine contraceptive system (LNG-IUS 13.5 mg; Jaydess®) and the etonogestrel subdermal contraceptive implant (ENG implant, Nexplanon®).

A multicenter, randomized phase III study comparing a 13.5 mg levonorgestrel intrauterine contraceptive system with a combined oral contraceptive: analysis of user satisfaction and safety

To compare user satisfaction and adverse events (AEs) with use of the 13.5 mg total content levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg) and a 30 μg ethinyl estradiol/3 mg drospirenone combined oral contraceptive (COC).

A multicenter, open-label, single-arm study exploring the safety of a new 13.5 mg total dose levonorgestrel intrauterine contraceptive system in postmenarcheal adolescents

To assess the safety profile of the 13.5 mg total content levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg; Skyla in the US, Jaydess elsewhere) over 1 year of use in postmenarcheal adolescents aged <18 years.

A phase III single-arm study of a new 13.5 mg levonorgestrel intrauterine contraceptive system in postmenarcheal adolescents: an evaluation of efficacy, bleeding, user satisfaction, and placement

To evaluate the efficacy, bleeding profile and user satisfaction associated with the 13.5 mg total content levonorgestrel intrauterine contraceptive system (LNG-IUS13.5mg; Skyla in the US, Jaydess elsewhere) in postmenarcheal adolescents, and to evaluate the placement of LNG-IUS13.5mg in this group. Safety (primary outcome) data are presented in another abstract.

The Japanese Ministry of Health, Labour and Welfare has approved Bayer Schering Pharma's levonorgestrel intrauterine contraceptive system [Mirena

The Japanese Ministry of Health, Labour and Welfare has approved Bayer Schering Pharma's levonorgestrel intrauterine contraceptive system [Mirena